This Mid-Career Investigator Award in Patient-Oriented Research (K24) proposes to foster research proficiency in: studying personality and mood;treatment development in children, adolescents, and adults at risk for depression;and refining academic leadership skills for the purpose of mentoring investigators while developing a Center for Intervention and Services Research (DCISR). The proposed Center will build an infrastructure to network investigators and to develop and test preventive interventions for patients with mood and related disorders. The career development and mentoring occur in the context of two randomized clinical trials (RCTs) evaluating the preventive effects of cognitive therapy (CT) in reducing the likelihood of mood disorders in adolescents at high risk for depression or in adult outpatients with high risk or refractory depression. The first trial is an ongoing multisite R01 in collaboration with the University of Pittsburgh Western Psychiatric Institute and Clinic. This blinded, controlled RCT will evaluate the efficacy of and indications for 8 months of continuation phase CT (C-CT), pharmacotherapy (the standard of care [FLX: fluoxetine]), and pill placebo (PBO: the control) in adult outpatients with recurrent major depressive disorder (MDD) who are at higher risk for relapse/recurrence. "Higher risk" is a score >6 on the Hamilton Rating Scale for Depression during the last 6 weeks of acute phase CT (A-CT), while "lower risk" is defined as a score of <=6. The primary hypothesis is that higher risk patients who receive either C-CT or FLX will have a longer time until relapse than higher risk patients who receive A-CT only plus PBO. The lower risk patients will be followed for 32 months without CT and are predicted to have a 20% relapse/recurrence rate in the first 8 months after A-CT. Approximately 724 male and female outpatients, aged 18-70, enter 16-20 sessions of A-CT. Responders will be randomized to either 8 months/10 sessions of (a) C-CT, (b) FLX, or (c) PBO. Protocol treatments are discontinued and follow-up lasts 2 more years. Relapse/recurrence (DSMIV MDD) is assessed by a blind evaluator using the Longitudinal Interval Follow-up Evaluation at 4, 8, 12, 16, 20, 24, 28, 32 months post A-CT and at suspected relapse/recurrence or exit. We predict the preventive effects of C-CT will endure longer than those of FLX or PBO. The second RTC will evaluate the efficacy of CT, mindfulness training, and treatment-as-usual in preventing first onset of depression in adolescents (ages 13-18) who are at risk for MDD because at least one of their parents was diagnosed with MDD. The research has great public health significance because it aims to identify when CT reduces the risk of first onset of depression or relapse/recurrence in patients suffering from recurrent MDD, an illness with high morbidity and mortality. Protected time for mentoring will allow the candidate to collaborate with beginning investigators to increase the pool of patient-oriented researchers.